Vegf-Mediated Angiogenesis In Retinopathy Of Prematurity Is Co-Regulated By Mir-17-5p And Mir-20a-5p

The microRNAs miR-17-5p and miR-20a-5p play important roles on angiogenesis; however, it is arguable whether they regulate the formation of retinal blood vessels in retinopathy of prematurity (ROP). We used a mouse model of oxygen-induced retinopathy (OIR) to simulate the development of retinas in mice suffering from ROP, and the expression levels of miR-20a-5p, miR-17-5p, hypoxia-inducible factor 1-alpha (HIF-1 alpha), and vascular endothelial growth factor (VEGF) were measured by RT-qPCR and Western blotting. Cell proliferation, apoptosis, and angiogenesis in the OIR model mice were measured using MTT assays, flow cytometry, and Matrigel assays, respectively. The interaction between HIF-1 alpha/VEGF and miR-20a-5p/miR-17-5p were further validated using dual-luciferase reporter assays, biotin-labeled RNA-pulldown, and RNA immunoprecipitation (RIP) assays. In our OIR model, retinal angiogenesis in the mice was associated with down-regulation of miR-20a-5p and miR-175p, as well as up-regulation of HIF-1 alpha and VEGF. In addition, the miR-20a-5p and miR-17-5p inhibited cell proliferation and angiogenesis through regulating HIF-1 alpha and VEGF in the retinal cells of the OIR model mice. Moreover, it was found that miR20a-5p and miR-17-5p bind to HIF-1 alpha and VEGF at the 3 0 UTR, and there was a combined effect between miR-20a-5p and miR-17-5p on the regulation of HIF-1 alpha and VEGF. It is worth noting that miR-17-5p and miR-20a-5p can preferentially regulate HIF-1 alpha, then act on VEGF, thereby affecting the angiogenesis associated with ROP.